Albumin and Alpha-fetoprotein (AFP) genes are tandemly arranged on human chromosome 4. However, the regulation of both genes is reciprocal after birth. In fact, AFP gene expression decreases to an almost undetectable level after birth ; in contrast, albumin gene expression remains high throughout life. The AFP gene is re-expressed in human hepatoma cells.In this study, the regulation of albumin and AFP genes by colloid osmotic pressure (COP), hepatocyte growth factor (HGF) and butyrate was analyzed using Northern blotting and CAT plasmid transfection assay. COP down-regulated both genes through the suppression of their promoter activities. HGF also repressed the AFP promoter activity, resulting in reduction of AFP mRNA level in a dose-dependent manner.Butyrate, a natural fermentation product of nomal colonic flora, inhibited cell growth in human hepatoma cells. Butyrate up-regulated the albumin gene expression, whereas it down-regulated the AFP gene expression through the modulation of their poromoter activities. Thus, it is possible that butyrate acts as a differentiation-inducer via the portal blood flow in human hepatoma cells.